Natural Product: NPC329401

Natural Product IDNPC329401
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Didehydrostemofoline
IUPAC Name n.a.
Synonyms 1',2'-Didehyrostemofoline
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1807141
PubChem CID 56666692
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0004603] Organic oxygen compounds
      • [CHEMONTID:0000323] Organooxygen compounds
        • [CHEMONTID:0000011] Carbohydrates and carbohydrate conjugates
          • [CHEMONTID:0003305] Aminosaccharides
            • [CHEMONTID:0000282] Aminoglycosides

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

  Chemical Representations

Standard InCHIKey XNUWGEPKIOWLHQ-KQYNXQAPSA-N
Standard InCHI InChI=1S/C22H27NO5/c1-5-6-8-21-14-7-9-23(21)13-10-15(21)27-22(14)16(13)11(2)18(28-22)19-17(25-4)12(3)20(24)26-19/h6,8,11,13-16H,5,7,9-10H2,1-4H3/b8-6+,19-18-/t11-,13-,14+,15-,16+,21-,22+/m0/s1
SMILES CCC=CC12C3CCN1C4CC2OC35C4C(C(=C6C(=C(C(=O)O6)C)OC)O5)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   385.19 Volume:   382.131
?
Van der Waals volume.
Dense:   1.008 LogP:   2.84
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.844
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.512
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   26.0
TPSA:   57.23
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   0.0 Rings:   6.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.55 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   7.102 Fsp3:   0.682
MCE-18:   123.919
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Rejected GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.156 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.036
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.283
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.026 Promiscuous compounds:   0.025

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.042 MDCK Permeability:   -4.9
Pgp-inhibitor:   0.082 Pgp-substrate:   0.096
PAMPA:   0.1
?
The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).
 Human Intestinal Absorption (HIA):   0.009
20% Bioavailability (F20%):   0.12 30% Bioavailability (F30%):   0.179
50% Bioavailability (F50%):   0.501

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.986 MRP1:   0.988
Plasma Protein Binding (PPB):   91.051% Volume Distribution (VD):   0.085
Fu: 7.861%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.261
OATP1B3 inhibitor:   0.571 BCRP inhibitor:   0.004
BSEP inhibitor:   0.941

ADMET: Metabolism

CYP1A2-inhibitor:   0.907 CYP1A2-substrate:   0.8
CYP2C19-inhibitor:   0.154 CYP2C19-substrate:   0.968
CYP2C9-inhibitor:   0.944 CYP2C9-substrate:   0.032
CYP2D6-inhibitor:   0.036 CYP2D6-substrate:   0.42
CYP3A4-inhibitor:   0.143 CYP3A4-substrate:   0.063
CYP2B6-substrate:   0.972 CYP2C8-inhibitor:   0.872
HLM stability:   0.885
?
Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):  8.091 Half-life (T1/2):  1.424

ADMET: Toxicity

hERG Blockers:  0.147 hERG Blockers (10um):  0.427
Human Hepatotoxicity (H-HT):  0.618 Drug-induced Liver Injury (DILI):  0.414
AMES Toxicity:  0.516 Rat Oral Acute Toxicity:  0.506
Maximum Recommended Daily Dose:  0.841 Skin Sensitization:  0.907
Carcinogencity:  0.294 Eye Corrosion:  0.0
Eye Irritation:  0.006 Respiratory Toxicity:  0.534
Drug-induced Neurotoxicity:  0.418 Ototoxicity:  0.857
Hematotoxicity:  0.164 Drug-induced Nephrotoxicity:  0.331
Genotoxicity:  0.822 RPMI-8226 Immunitoxicity:  0.093
A549 Cytotoxicity:  0.023 Hek293 Cytotoxicity:  0.364
BCF:   1.767
?
Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].
 IGC50:   4.494
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.924
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.553
?
96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

  Species Source

Organism ID Organism Name Taxonomy Level Family SuperKingdom Isolation Part Collection Location Collection Time Reference
NPO1235 Stemona curtisii Species Stemonaceae Eukaryota n.a. n.a. n.a. PMID[15104502]
NPO1235 Stemona curtisii Species Stemonaceae Eukaryota n.a. n.a. n.a. PMID[21049906]
NPO1235 Stemona curtisii Species Stemonaceae Eukaryota n.a. root n.a. PMID[21049906]
NPO1235 Stemona curtisii Species Stemonaceae Eukaryota n.a. rhizome n.a. PMID[21902195]
NPO1235 Stemona curtisii Species Stemonaceae Eukaryota n.a. tuberous root n.a. PMID[21902195]
NPO1235 Stemona curtisii Species Stemonaceae Eukaryota n.a. n.a. n.a. PMID[21902195]
NPO1235 Stemona curtisii Species Stemonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1235 Stemona curtisii Species Stemonaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO1235 Stemona curtisii Species Stemonaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO1235 Stemona curtisii Species Stemonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]

Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].



  NP Quantity Composition/Concentration

Organism ID Organism Name Organism Material Preparation Organism Part NP Quantity (Standard) NP Quantity (Minimum) NP Quantity (Maximum) Quantity Unit Reference

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].



 Biological Activity

Molecular-level activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT204 Individual protein Acetylcholinesterase Homo sapiens MIC = 5.0 ng PMID[21126060]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference





 Experimental ADME

Experiment Model Experiment Tissue ADME Type ADME Relation ADME Value ADME Unit Reference





 Experimental Toxicity

Quantitative toxicity

Experiment Model Experiment Organism Toxicity Type Toxicity Relation Toxicity Value Toxicity Unit Reference
- Spodoptera littoralis LC50 = 0.84 ppm PMID[12381121]
- Spodoptera littoralis LC50 = 0.46 ppm PMID[12381121]
- Spodoptera littoralis LC50 = 1.01 microg/dm2 PMID[12381121]

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity Carcinogenicity Mutagenicity Cardiotoxicity Respiratory Toxicity Eye Irritation Endocrine Disruption
Hepatotoxicity Carcinogenicity Mutagenicity Cardiotoxicity Respiratory Toxicity Eye Irritation Endocrine Disruption

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]


  Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

●  The left chart: Distribution of similarity level between NPC329401 and all remaining natural products in the NPASS database.
●  The right table: Most similar natural products (Tc>=0.5 or Top200).

Similarity Score Similarity Level Natural Product ID
1.0 High Similarity NPC477987
0.8676 High Similarity NPC486944
0.8676 High Similarity NPC486947
0.8382 Intermediate Similarity NPC486949
0.8382 Intermediate Similarity NPC486952
0.8382 Intermediate Similarity NPC486946
0.8261 Intermediate Similarity NPC486930
0.8143 Intermediate Similarity NPC486929
0.7576 Intermediate Similarity NPC477986
0.7143 Intermediate Similarity NPC138534
0.7143 Intermediate Similarity NPC486938
0.7143 Intermediate Similarity NPC486937
0.6892 Remote Similarity NPC486939
0.6892 Remote Similarity NPC486936
0.6892 Remote Similarity NPC486945
0.6892 Remote Similarity NPC486940
0.6849 Remote Similarity NPC486932
0.6849 Remote Similarity NPC323168
0.6849 Remote Similarity NPC486935
0.6849 Remote Similarity NPC486934
0.6849 Remote Similarity NPC486948
0.6849 Remote Similarity NPC486931
0.6849 Remote Similarity NPC111162
0.6849 Remote Similarity NPC486933
0.6849 Remote Similarity NPC486941
0.6849 Remote Similarity NPC486928
0.6849 Remote Similarity NPC293550
0.6667 Remote Similarity NPC486942
0.6667 Remote Similarity NPC486943

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

●  The left chart: Distribution of similarity level between NPC329401 and all drugs/candidates.
●  The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

Similarity Score Similarity Level Drug ID Developmental Stage
NPD

Bioactivity similarity

  Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.
Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity
B: biological targets similarity
C: networks similarity
D: cell-based bioactivity similarity
E: similarity based on clinical data